The key objective of this study is to collect the first nationally representative data on prevalences and correlates of DSM-IV MDD from the recently completed National Comorbidity Survey Replication (NCS-R). The study design is a direct interview household survey of a probability household survey of adults ages 18 and over from the 48 contiguous United States. The total number of subjects in the study is 9090, representing a 79% response rate. The diagnostic interview was the WHO Composite International Diagnostic Interview (CIDI), developed to collect diagnostic criteria for the DSM-IV. Clinical re-interviews were carried out with the Structured Clinical Interview for DSM-IV (SCID) to validate CIDI diagnoses. The NCS research program consists of a series of surveys associated with the U.S. National Comorbidity Survey (NCS). The baseline NCS, fielded from the fall of 1990 to the spring of 1992, was the first nationally representative mental health survey in the U.S. to use a fully structured research diagnostic interview to assess the prevalences and correlates of DSM-III-R disorders. The baseline NCS respondents were reinterviewed in 2001-02 (NCS-2) to study patterns and predictors of the course of mental and substance use disorders and to evaluate the effects of primary mental disorders in predicting the onset and course of secondary substance disorders. In conjunction with this, an NCS Replication survey (NCS-R) was carried out in a new national sample of 10,000 respondents. The goals of NCS-R are to study trends in a wide range of variables assessed in the baseline NCS and to obtain more information about a number of topics either not covered in the baseline NCS or covered in less depth than we currently desire. A survey of 10,000 adolescents (NCS-A) is being carried out in parallel with the NCS-R and NCS-2 surveys. The goal of NCS-A is to produce nationally representative data on the prevalences and correlates of mental disorders among youth. NCS-R and NCS-A, finally, are being replicated in a number of countries around the world. Centralized cross-national analysis of these surveys is being carried out by the NCS data analysis team under the auspices of the World Health Organization World Mental Health Survey Initiative. The NCS-R field study was completed in the fall of 2003. After one and one-half years of data processing, development of diagnostic algorithms and complex weighting procedures, the first prevalence papers from the NCS-A were published in June of 2005 . We have been involved in the work on the major themes of our research including mood disorders and mental and physical comorbidity. The major findings of this work that are relevant to our research are that there is a spectrum of expression of bipolar disorder in the population with evidence for clinical validity of sub-threshold bipolar disorder; comorbidity between bipolar disorder and other mental disorders is dramatically elevated such that nearly two-thirds of bipolars have a substance use disorder; using a novel analytic method that accounts for comorbidity, we estimated the comparative effects of common mental and physical conditions on role disability in the general population. After controlling for comorbidity, we found that mental conditions account for more than half as many disability days as all physical conditions at the population level; eighty-five percent of migraineurs in the general population have at least one other lifetime mental or physical disorder. Comorbidity explained more than half the role disability associated with migraine. There is a spectrum of expression of mood disorders such that those with mild disorders have a high probability of recurrence across a decade of follow up.